In many pathological conditions, there is an imbalance in the partition of fluid and solutes between the vascular and extravascular spaces. Changes in the hydration of the interstitial gel matrix will effect the distribution of plasma proteins between these two compartments and alter the fluid distribution. The general aim of the proposed study is to determine changes in the distribution and transport of plasma proteins in the interstitium of skin and skeletal muscle and relate the data to the present concepts on the control of fluid balance in the body. My previous studies indicate that the extravascular distribution of plasma proteins in skin and skeletal muscle following saline expansion or plasmapheresis is different from that following increased venous pressure or increased capillary wall permeability. This may have important consequences on the fluid balance between the vascular and interstitial spaces since the major fraction of the total body interstitial fluid is represented by skin and skeletal muscle. I propose to test the hypothesis that plasma proteins are carried directly from plasma to lymph through free fluid channels within the interstitium following venous congestion or altered endothelial permeability and through the interstitial gel matrix following plasmapheresis. I will study this in both skin and skeletal muscle in the hind leg of anesthetized rabbits. I will compare the equilibration rate for tracer albumin in the interstitium to that in lymph to determine whether albumin is transported through free fluid channels or through the gel matrix. I will also determine the effects of different forms of edema on electrostatic exclusion of albumin. This will be done by studying the extravascular transport and distribution of tracer albumin, which has an altered charge but not size. Additional studies will compare the effects of hyperproteinemia to those of hypoproteinemia on the extravascular distribution of fluid and plasma proteins in skin and skeletal muscle. These results will provide information on the role of the interstitial matrix in tissue fluid balance as well as provide insight into the etiology of edema formation.